The songbird model system has made novel and important contributions to a number of areas of neurobiological research, and stands as one of the most powerful models for studying the role of gone regulation in neural plasticity. The goal of this proposal is to apply powerful new methods of genomics to the further study and development of this model. A consortium of seven songbird investigators, at six different institutions in the U.S., will work with the Keck Center for Comparative and Functional Genomics at the University of Illinois, to establish: a) a collection of cDNA clones representing the mRNAs in the zebra finch brain; b) a database of expressed sequence tags (ESTs) derived by high-throughput sequencing of the collection; c) a web-based publicly accessible server for analysis of the EST database; d) generations of glass microarrays containing a "unigene" set of ESTs plus control DNAs; e) optimized protocols for hybridization of microarrays with RNA probes derived from zebra finches and other songbirds. All these resources will be made available to the larger scientific community at low cost. The consortium will specifically apply these tools to a range of objectives defined in their currently-funded research programs. Additionally, pilot experiments will be conducted to confirm and extend four aspects of differential gene expression in the zebra finch brain: 1) gene induction associated with song perceptual learning in adults; 2) gene regulation within specific song nuclei during the critical period for song learning in juveniles (a paradigm specifically relevant to functional study of the Parkinson's Disease-linked gene, alpha-synuclein); 3) differential expression of song nucleus-specific or enriched genes; 4) differential expression of genes associated with brain sexual differentiation. To encourage refinement and widespread use of these resources, a periodic workshop for all interested investigators will be organized, and an Advisory Board representing the larger songbird research community will be appointed and consulted regularly. A key aspect of this proposal is the application of the cost-effective and proven resources of the Keck Center, which have been successfully used to develop similar genomics toolsets for other non-mainstream model organisms, including honeybees and cattle. This project will have both immediate and long-term consequences for research into a number of issues relevant to human health and disease, including molecular mechanisms involved in learning, control of sexual differentiation, effects of steroids on brain function and development, and processes that promote or limit brain cellular plasticity and repair. [unreadable] [unreadable]